PMID- 33974808
OWN - NLM
STAT- MEDLINE
DCOM- 20220103
LR  - 20220103
IS  - 1208-6002 (Electronic)
IS  - 0829-8211 (Linking)
VI  - 99
IP  - 5
DP  - 2021 Oct
TI  - Saikosaponin-d protects against liver fibrosis by regulating the estrogen 
      receptor-beta/NLRP3 inflammasome pathway.
PG  - 666-674
LID - 10.1139/bcb-2020-0561 [doi]
AB  - Liver fibrosis is the most common pathway in most types of chronic liver damage, 
      characterized by an imbalance of ECM degradation and synthesis. Saikosaponin-d 
      (SSd) possesses anti-inflammatory and anti-fibrotic effects. However, the 
      underlying mechanism by which SSd represses hepatic stellate cell (HSC) 
      activation remains unclear. Here, we found that SSd remarkably alleviated carbon 
      tetrachloride (CCl(4))-induced liver fibrosis, as evidenced by decreased collagen 
      levels and profibrotic marker (COl1a1 and alpha-smooth muscle actin (SMA)) 
      expression. SSd repressed CCl(4)-induced NOD-like receptor family 
      pyrin-domain-containing-3 (NLRP3) activation in fibrotic livers, as suggested by 
      decreased levels of NLRP3, IL-18, and IL-beta. The primary HSCs of CCl(4) mice 
      exhibited a significant increase in profibrotic marker expression and NLRP3 
      activation, but SSd treatment reversed this effect. SSd also repressed 
      TGF-beta-induced profibrotic marker expression and NLRP3 activation in vitro. 
      Mechanistically, TGF-beta decreased the expression of estrogen receptor-beta (ERbeta) in 
      HSCs, whereas SSd treatment reversed this effect. ERbeta inhibition enhances NLRP3 
      activation in HSCs. More importantly, ERbeta or NLRP3 inhibition partially destroyed 
      the function of SSd in liver fibrosis. In summary, the current data suggest that 
      SSd prevents hepatic fibrosis by regulating the ERbeta/NLRP3 inflammasome pathway 
      and suggests SSd as a potential agent for treating liver fibrosis.
FAU - Lin, Liubing
AU  - Lin L
AD  - Department of Gastroenterology, Shanghai Municipal Hospital of Traditional 
      Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 
      China.
FAU - Zhou, Mengen
AU  - Zhou M
AD  - Department of Gastroenterology, Shanghai Municipal Hospital of Traditional 
      Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 
      China.
FAU - Que, Renye
AU  - Que R
AD  - Department of Gastroenterology, Shanghai TCM Integrated Hospital, Shanghai 
      University of Traditional Chinese Medicine, Shanghai, China.
FAU - Chen, Yirong
AU  - Chen Y
AD  - Department of Gastroenterology, Shanghai Municipal Hospital of Traditional 
      Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 
      China.
FAU - Liu, Xiaolin
AU  - Liu X
AD  - Department of Gastroenterology, Shanghai Municipal Hospital of Traditional 
      Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 
      China.
FAU - Zhang, Kehui
AU  - Zhang K
AD  - Department of Gastroenterology, Shanghai Municipal Hospital of Traditional 
      Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 
      China.
FAU - Shi, Zhe
AU  - Shi Z
AD  - Department of Gastroenterology, Shanghai Municipal Hospital of Traditional 
      Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 
      China.
FAU - Li, Yong
AU  - Li Y
AD  - Department of Gastroenterology, Shanghai Municipal Hospital of Traditional 
      Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210511
PL  - Canada
TA  - Biochem Cell Biol
JT  - Biochemistry and cell biology = Biochimie et biologie cellulaire
JID - 8606068
RN  - 0 (Estrogen Receptor beta)
RN  - 0 (Inflammasomes)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Nlrp3 protein, mouse)
RN  - 0 (Protective Agents)
RN  - 0 (Saponins)
RN  - 6SMK8R7TGJ (Oleanolic Acid)
RN  - CL2T97X0V0 (Carbon Tetrachloride)
RN  - UR635J3F00 (saikosaponin D)
SB  - IM
MH  - Animals
MH  - Carbon Tetrachloride
MH  - Cells, Cultured
MH  - Estrogen Receptor beta/*antagonists & inhibitors/metabolism
MH  - Inflammasomes/*drug effects/metabolism
MH  - Liver Cirrhosis/chemically induced/*drug therapy/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/*antagonists & 
      inhibitors/metabolism
MH  - Oleanolic Acid/*analogs & derivatives/pharmacology
MH  - Protective Agents/*pharmacology
MH  - Saponins/*pharmacology
OTO - NOTNLM
OT  - NLRP3 inflammasome
OT  - cellules de Kupffer
OT  - estrogen receptor-beta
OT  - fibrose hepatique
OT  - hepatic stellate cells
OT  - inflammasome NLRP3
OT  - liver fibrosis
OT  - recepteur des oestrogenes-beta
OT  - saikosaponin-d
OT  - saikosaponine-d
EDAT- 2021/05/12 06:00
MHDA- 2022/01/04 06:00
CRDT- 2021/05/11 20:09
PHST- 2021/05/12 06:00 [pubmed]
PHST- 2022/01/04 06:00 [medline]
PHST- 2021/05/11 20:09 [entrez]
AID - 10.1139/bcb-2020-0561 [doi]
PST - ppublish
SO  - Biochem Cell Biol. 2021 Oct;99(5):666-674. doi: 10.1139/bcb-2020-0561. Epub 2021 
      May 11.